Graft-versus-host-diseasePhase 1NCT03605927
CD40-L Blockade for Prevention of Acute Graft-Versus-Host Disease
A Phase 1 study testing BMS-986004, Sirolimus and Tacrolimus in people with Graft-versus-host-disease and GVHD, run by H. Lee Moffitt Cancer Center and Research Institute at 3 sites in United States.
Trial summary
The purpose of this study is to examine the safety and efficacy of the addition of BMS-986004 to standard of care Sirolimus (SIR)-based immune suppression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft-versus-host-disease, GVHD, GVHD, Acute
- What is being tested?
- BMS-986004, Sirolimus and Tacrolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 3 sitesUnited States
- Study dates
- 15 Feb 2019to 25 Jul 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hematologic malignancy or blood disorder requiring allogeneic HCT
- Adequate vital organ function as defined per protocol
- Karnofsky Performance Status Score (KPS) ≥ 80%
- Participants must have an available 8/8 HLA-A, -B, -C, and -DRB1 matched-related or unrelated donor
Who cannot join
- Active infection not controlled with appropriate antimicrobial therapy
- HIV, hepatitis B or C infection or known history of HIV, hepatitis B or C(all patients will be tested for HIV, hepatitis B and C as part of standard pre-transplant testing, and will be excluded from this trial if positive)
- Anti-thymocyte globulin, or cyclophosphamide administered within 14 days before or planned to receive with HCT conditioning or as part of GVHD prophylaxis in the 14 days after HCT
- Known allergic reactions to components of the study drug
- Concurrent treatment with another investigational drug
- History of thromboembolism, transient ischemic attack, stroke, myocardial infarction within 3 months preceding the transplant, or uncontrolled congestive heart failure or cardiac arrhythmias.
- Post-transplant maintenance therapies such as FLT3 inhibitor, tyrosine kinase inhibitor, JAK inhibitors etc. are not allowed if plan is to initiate such therapies <90 days post-transplant. Patient will be eligible if plan to initiate maintenance therapy is after day 90 post-transplant.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
City of Hope Cancer Center
Duarte, California, 91010
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
The purpose of this study is to examine the safety and efficacy of the addition of BMS-986004 to standard of care Sirolimus (SIR)-based immune suppression.
Read the detailed description
The approach builds upon extensive evidence supporting the benefit of CD40L blockade in disrupting key signaling events associated with immune activation. The trial addresses a pressing clinical need, namely prevention of Graft-Versus-Host Disease (GVHD) after hematopoietic cell transplantation (HCT) and promotion of donor-recipient immune tolerance. The safety profile of this anti-CD40L antibody overcomes major prior limitations, and the planned biologic studies will provide significant mechanistic insight.
- Conditions
- Graft-versus-host-disease, GVHD, GVHD, Acute
- Being tested
- BMS-986004, Sirolimus, Tacrolimus
- Keywords
- HCT, hematopoietic cell transplantation, antibody therapy
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-986004Drug
Also called Anti-CD40L Domain Antibody
BMS-986004 will be administered in ascending dose cohorts in the phase I component of the trial. Based on prior PK and PD data, dose levels of 225 mg, 675 mg, and 1500 mg (3 total phase I dose levels) will be examined. BMS-986004 will be given intravenously (IV) every 2 weeks, starting from day -3 (i.e., three days prior to HCT) onward through a total of 100 days post-HCT. The maximum tolerated dose (MTD) identified in the phase I component of the trial will be carried forward as the recommended dose level in the phase 1 expansion cohort.
SirolimusDrug
Also called Standard of Care, SIR
Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards.
Sirolimus (SIR) will be given as a loading dose on day -1 orally, then daily as maintenance therapy with target levels of 10-14ng/mL early post-HCT, then tapered to 5-14ng/mL range.
Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions.
TacrolimusDrug
Also called Standard of Care, TAC
Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards.
In brief, tacrolimus (TAC) will be started on day -3 IV, and transitioned to oral TAC when oral medications are tolerated; target level is 3-7ng/mL.
Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions.
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Experimental | BMS-986004: From day 13, intravenously (IV) every 2 week through day 100 post HCT.
Tacrolimus: From day -3 as standard of care. Sirolimus: From day -1 as standard of care. Receives: Drug: BMS-986004; Drug: Sirolimus; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Grade II-IV Acute Graft-versus Host Disease
Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) by day 100 after hematopoietic cell transplantation (HCT). Acute GVHD severity will be determined by standard Consensus Criteria, and the cumulative incidence of grade II-IV acute GVHD will be reported through day 100 post-HCT, with relapse and death as competing risk events.
Measured: 1 year post HCT
Secondary outcomes (4)
Chronic Graft-versus Host Disease Through 1 Year Post HCT
NIH criteria defined chronic graft-versus-host disease through 1 year post-HCT. Chronic GVHD will be defined by the presence of chronic GVHD defining features, regardless of time post-HCT, in keeping with the NIH Consensus Criteria on diagnosis and staging of chronic GVHD. Individual affected organs are staged on 0-3 severity scale, and summarized for an overall global severity score. The presence of acute GVHD features defines the following subgroups: (1) late acute GVHD (sole presence of acute GVHD features after day 100 post-HCT), (2) overlap subtype of chronic GVHD (co-occurrence of chronic and acute GVHD features, and (3) classic chronic GVHD (absence of concurrent acute GVHD features).
Measured: 1 year post HCT
Malignancy Relapse Post-HCT
Defined as hematologic relapse or any unplanned intervention (including withdrawal of immune suppression) to prevent progression of disease in patients with evidence (molecular, cytogenetic, flow cytometric, radiographic) of malignant disease after HCT.
Measured: 1 year post HCT
Non-relapse Mortality
Defined as death in the absence of malignancy relapse post-HCT.
Measured: 1 year post HCT
Overall Survival (OS)
Defined as time from HCT to death or censoring for last follow up.
Measured: 1 year post HCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2018
- Study start15 Feb 2019
- Primary completion25 Jul 2023
- Study completion25 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft-versus-host-diseaseStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Farhad Khimani, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03605927
- Sponsor's protocol ID
- MCC-19305
- Status last verified
- Mar 2026
- First submitted
- 20 Jul 2018
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD40-L Blockade for Prevention of Acute Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT03605927
- Acronym / sponsor ID
- MCC-19305
- Conditions
- Graft-versus-host-disease, GVHD, GVHD, Acute
- Keywords
- HCT, hematopoietic cell transplantation, antibody therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 15 Feb 2019 (actual)
- Primary completion
- 25 Jul 2023 (actual)
- Study completion
- 25 Jul 2023 (actual)
- First posted
- 30 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to examine the safety and efficacy of the addition of BMS-986004 to standard of care Sirolimus (SIR)-based immune suppression.
Detailed description
The approach builds upon extensive evidence supporting the benefit of CD40L blockade in disrupting key signaling events associated with immune activation. The trial addresses a pressing clinical need, namely prevention of Graft-Versus-Host Disease (GVHD) after hematopoietic cell transplantation (HCT) and promotion of donor-recipient immune tolerance. The safety profile of this anti-CD40L antibody overcomes major prior limitations, and the planned biologic studies will provide significant mechanistic insight.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy | Experimental | Drug: BMS-986004, Drug: Sirolimus, Drug: TacrolimusBMS-986004: From day 13, intravenously (IV) every 2 week through day 100 post HCT. Tacrolimus: From day -3 as standard of care. Sirolimus: From day -1 as standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Hematologic malignancy or blood disorder requiring allogeneic HCT
- Adequate vital organ function as defined per protocol
- Karnofsky Performance Status Score (KPS) ≥ 80%
- Participants must have an available 8/8 HLA-A, -B, -C, and -DRB1 matched-related or unrelated donor
Key exclusion criteria (7 listed)
- Active infection not controlled with appropriate antimicrobial therapy
- HIV, hepatitis B or C infection or known history of HIV, hepatitis B or C(all patients will be tested for HIV, hepatitis B and C as part of standard pre-transplant testing, and will be excluded from this trial if positive)
- Anti-thymocyte globulin, or cyclophosphamide administered within 14 days before or planned to receive with HCT conditioning or as part of GVHD prophylaxis in the 14 days after HCT
- Known allergic reactions to components of the study drug
- Concurrent treatment with another investigational drug
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMS-986004Also: Anti-CD40L Domain AntibodyBMS-986004 will be administered in ascending dose cohorts in the phase I component of the trial. Based on prior PK and PD data, dose levels of 225 mg, 675 mg, and 1500 mg (3 total phase I dose levels) will be examined. BMS-986004 will be given intravenously (IV) every 2 weeks, starting from day -3 (i.e., three days prior to HCT) onward through a total of 100 days post-HCT. The maximum tolerated dose (MTD) identified in the phase I component of the trial will be carried forward as the recommended dose level in the phase 1 expansion cohort. | Drug | Combination Therapy |
| SirolimusAlso: Standard of Care, SIRSirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards. Sirolimus (SIR) will be given as a loading dose on day -1 orally, then daily as maintenance therapy with target levels of 10-14ng/mL early post-HCT, then tapered to 5-14ng/mL range. Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions. | Drug | Combination Therapy |
| TacrolimusAlso: Standard of Care, TACSirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards. In brief, tacrolimus (TAC) will be started on day -3 IV, and transitioned to oral TAC when oral medications are tolerated; target level is 3-7ng/mL. Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions. | Drug | Combination Therapy |
Primary outcome
Incidence of Grade II-IV Acute Graft-versus Host Disease
Time frame: 1 year post HCT
Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) by day 100 after hematopoietic cell transplantation (HCT). Acute GVHD severity will be determined by standard Consensus Criteria, and the cumulative incidence of grade II-IV acute GVHD will be reported through day 100 post-HCT, with relapse and death as competing risk events.
4 secondary outcomes
Chronic Graft-versus Host Disease Through 1 Year Post HCT
Time frame: 1 year post HCT
Malignancy Relapse Post-HCT
Time frame: 1 year post HCT
Non-relapse Mortality
Time frame: 1 year post HCT
Overall Survival (OS)
Time frame: 1 year post HCT
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
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Graft vs Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Farhad Khimani, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMS-986004, Sirolimus and Tacrolimus in people with Graft-versus-host-disease and GVHD, run by H. Lee Moffitt Cancer Center and Research Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Grade II-IV Acute Graft-versus Host Disease (time frame: 1 year post HCT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.